免疫反进化:不朽化的B细胞克隆可以经历ex vivo定向进化以抵消病毒逃逸
Casper Marsman1, Jurgen Heinen1, Vanessa Clerico Mosina1
1Kling Biotherapeutics, Amsterdam, Netherlands.
Frontiers in immunology
|September 3, 2025
概括
这项研究开发了不朽的B细胞库,并指导进化产生有效的抗体来对抗不断演变的SARS-CoV-2变种,包括JN.1等免疫逃生菌株.
科学领域:
- 免疫学
- 病毒学
- 生物技术
背景情况:
- SARS-CoV-2 的演变给疫苗和治疗疗效带来了挑战.
- 免疫逃生变体的出现需要快速开发可适应的对策.
研究的目的:
- 利用不朽化B细胞库识别针对SARS-CoV-2变种的交叉反应中和抗体.
- 应用定向进化来增强对新出现的SARS-CoV-2变种的抗体结合和中和效力.
主要方法:
- 使用逆转录病毒载体从PBMC和桃体中取出人类B细胞.
- 对B细胞库进行高通量选以识别中和克隆.
- 通过体质突变引导出体进化以提高抗体亲和力和交叉反应力.
- 两种类型抗体的工程结合中和广泛结合的抗体.
主要成果:
- 确定了12种具有SARS-CoV-2中和活性的独特B细胞克隆.
- 开发出具有强大中和能力的单克隆抗体来对抗Delta和BA.5变种.
- 针对EG.5.1和JN.1免疫逃生变体增强了抗体效力.
- 针对JN.1和KP.3变种的抗体增强.
结论:
- 不朽化的B细胞库和定向进化对于开发抗病毒疗法的有效.
- 这种方法为制造适应性抗体应对新出现的SARS-CoV-2变种提供了快速的途径.
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